PROJECT SUMMARY The uveitides are a collection of diseases characterized by intraocular inflammation. Collectively, they are the 5th leading cause of blindness in the US, and the estimated cost of treating them is similar to that of treating diabetic retinopathy. Non-infectious intermediate, posterior, and panuveitides have the highest rates of visual loss and typically are treated with oral corticosteroids and immunosuppression. The Multicenter Uveitis Steroid Treatment (MUST) Trial (a randomized, comparative effectiveness trial, which compared 2 treatment paradigms for these diseases, systemic therapy with corticosteroids and immunosuppression vs. regional therapy [the fluocinolone acetonide implant]), and Follow-up Study demonstrated the superiority of the systemic approach to the regional ocular approach in terms of long-term visual outcomes with essentially no increase in systemic side effects in the systemic group. One key to systemic therapy's success was the use of systemic immunosuppression in 88% of participants, coupled with tapering the prednisone to <7.5 mg/day, a relatively safe dose. The drugs used most often used are azathioprine, methotrexate, mycophenolate, cyclosporine, and tacrolimus. The alkylating agents, cyclophosphamide and chlorambucil, are used less often because of concerns about potential increased malignancy risk. Available data suggest that single-agent conventional, non-alkylating-agent, immunosuppressive drugs are effective in controlling the inflammation while permitting tapering prednisone to <10 mg/day in ~40-55% of patients; hence, combination therapy often is needed. Minimizing the daily dose of prednisone is important, as the risk of cardiovascular disease and mortality increases with the cumulative dose of oral corticosteroids. In June 2016, the fully-human, anti-TNF-? monoclonal antibody, adalimumab, was approved by the US Food and Drug Administration (FDA) for the treatment of uveitis. Anti-TNF-? monoclonal antibody therapy has revolutionized the management of the rheumatic diseases largely due to its superior efficacy compared to conventional Disease Modifying Anti- Rheumatic Drugs. Data from VISUAL III, the extension of the two phase 3 trials that led to the FDA approval of adalimumab for the treatment of uveitis, suggest that adalimumab may be superior to conventional immunosuppression, as ~75% of participants had controlled inflammation with prednisone doses <5 mg/day sustained through 1 year of follow-up. The ADalimumab Vs. conventional ImmunoSupprEssion for uveitis (ADVISE) Trial is a randomized, comparative effectiveness trial comparing adalimumab to conventional agent immunosuppression for patients with non-infectious, intermediate, posterior, and panuveitides. The primary outcome is the ability to successfully taper prednisone to <7.5 mg/day by 6 months after randomization while maintaining control of the inflammation. Secondary outcomes include prednisone discontinuation with inflammation control by 1 year, visual acuity, and incident complications of uveitis and its treatment.